ArticleeLife2022
GFPT2/GFAT2 and AMDHD2 act in tandem to control the hexosamine pathway.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Multi-omics analysis of glutamine and fish collagen peptides in alleviating post-antibioticExperimental and therapeutic medicine · 2026Article
- GFPT2 promotes macrophage dysfunction in atherosclerosis via ACADL glycosylation-dependent suppression of ACADL and Arg1.Cellular and molecular life sciences : CMLS · 2026Article
- Comprehensive CRISPR/Cas9-based mutagenesis identifies single-amino acid substitutions that abrogate SPEN function in X inactivation.Nature communications · 2026Article
- Molecular characteristics of follicular fluid in advanced maternal age women with different ovarian reserves: a multi-omics study.BMC women's health · 2026Article
- Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants.GeroScience · 2026Article
- Article
- ThemicroPublication biology · 2026Article
- GFPT2 drives sunitinib resistance of renal cell carcinoma via enzyme-dependent and -independent manners.International journal of biological sciences · 2026Article
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease.Molecular neurobiology · 2025Review
- Structural Basis for Tetramerization ofJournal of microbiology and biotechnology · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Integrated multi-omics characterization across clinically relevant subgroups of long COVID.National science review · 2025Article
- Mechanisms on How Matricellular Microenvironments Sustain Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- Methylseq, single-nuclei RNAseq, and discovery proteomics identify pathways associated with nephron-deficit CKD in the HSRA rat model.American journal of physiology. Renal physiology · 2025Article
- The Prognostic Value and Immunotherapeutic Characteristics of GFPT2 in Pan-cancer.Combinatorial chemistry & high throughput screening · 2025Article
- Identifying KL-6-Associated Immune Cell Signatures and Key Genes in Emphysematous COPD.Journal of inflammation research · 2025Article
- The role of protein O-GlcNAcylation in diabetic cardiomyopathy.Biochemical Society transactions · 2024Review
- GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression.British journal of cancer · 2024Article
- Functional Insights into the Sphingolipids C1P, S1P, and SPC in Human Fibroblast-like Synoviocytes by Proteomic Analysis.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hexosamine biosynthetic pathway (HBP) produces the essential metabolite UDP-GlcNAc and plays a key role in metabolism, health, and aging. The HBP is controlled by its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFPT/GFAT) that is directly inhibited by UDP-GlcNAc in a feedback loop. HBP regulation by GFPT is well studied but other HBP regulators have remained obscure. Elevated UDP-GlcNAc levels counteract the glycosylation toxin tunicamycin (TM), and thus we screened for TM resistance in haploid mouse embryonic stem cells (mESCs) using random chemical mutagenesis to determine alternative HBP regulation. We identified the N-acetylglucosamine deacetylase AMDHD2 that catalyzes a reverse reaction in the HBP and its loss strongly elevated UDP-GlcNAc. To better understand AMDHD2, we solved the crystal structure and found that loss-of-function (LOF) is caused by protein destabilization or interference with its catalytic activity. Finally, we show that mESCs express AMDHD2 together with GFPT2 instead of the more common paralog GFPT1. Compared with GFPT1, GFPT2 had a much lower sensitivity to UDP-GlcNAc inhibition, explaining how AMDHD2 LOF resulted in HBP activation. This HBP configuration in which AMDHD2 serves to balance GFPT2 activity was also observed in other mESCs and, consistently, the GFPT2:GFPT1 ratio decreased with differentiation of human embryonic stem cells. Taken together, our data reveal a critical function of AMDHD2 in limiting UDP-GlcNAc production in cells that use GFPT2 for metabolite entry into the HBP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.